Top of Form

Bottom of Form

Published 26 February 2009

Cite this as: BMJ Case Reports 2009 [doi:10.1136/bcr.06.2008.0033]

Copyright © 2009 by the BMJ Publishing Group Ltd.

Unexpected outcome (positive or negative) including adverse drug reactions

Transient global amnesia associated with statin intake

David Healy1, Roger Morgan2 and Srinivasan Chinnaswamy2

1 Cardiff University, Psychological Medicine, Hergest Unit, Bangor, LL57 2PW, U K
2 North West Wales NHS Trust, Mental Health, Bangor, LL57 2PW, UK

Correspondence to:

SUMMARY

A 57-year-old man treated with statins developed a range of amnestic features that led to concerns he might be suicidal; however, he did not appear to have depression. His problems began after starting rosuvastatin and cleared on discontinuation.

BACKGROUND

The difficulties this man had were striking. It seems likely given his response to treatment that this condition was linked to his statin intake, but there is little literature on statin-related problems of this type and accordingly it is unlikely that the correct diagnosis would commonly be made. This report attempts to remedy a gap in the literature.

CASE PRESENTATION

A 57-year-old man presented with end-stage renal failure secondary to hypertensive nephropathy. In 2001, he was started on dialysis for renal failure. He continued to work. At this point he was on lisinopril and amlodipine for blood pressure and was started on 40 mg simvastatin.

His worsening condition in 2004 led to unhappiness. His primary care doctor prescribed dosulepin later changing this to sertraline. His simvastatin was changed to 10 mg rosuvastatin in December 2004. Prior to this, his cholesterol level had tracked at 4.5–5.0 mmol/L but had jumped to 6.3 mmol/L. On rosuvastatin his cholesterol level in February 2005 was 3.0 mmol/L.

The medical notes contain no mention of confusion prior to February 2005. In February 2005, two episodes were noted. In one, he had made 40 cups of tea but could later give no reason for this other than he must have been dreaming of having guests to the house. In the other, during home dialysis he had cut the lines into the dialysis machine with a pair of scissors. He vaguely remembered freeing himself from the lines and retiring to bed.

This latter incident and concerns that he might be drinking more water than advised led to a referral to the psychiatric liaison service in August 2005 because of possible self-harm. He denied thoughts of self-harm. But he described feeling that there were further episodes of behaviours for which he had no recall. Psychiatric assessment found no evidence of psychotic or delirious phenomena. He was not depressed. He scored 28/30 on Mini Mental State.

In September, the patient’s wife reported that he was having episodes when he was uncertain where he was or what he was supposed to be doing. He complained of feeling disorganised at these times.

He was expecting to lose his job and was later obliged to retire against his wishes on ill-health grounds. He was unhappy at losing his job but further psychiatric assessment found no evidence of depression or psychosis.

The possibilities of transient ischaemic attacks or other metabolic disturbances were considered as possible triggers for the episodes he was having. Physical examination was normal. There was no evidence of focal neurological abnormality. An electroencephalogram was normal. Routine blood tests were normal. Cognitive function testing showed no abnormality.

In November 2005, after retirement, the patient was again referred to the liaison service complaining of flashbacks from his military experience after watching a war film. At this point, he complained that he was lacking direction and losing time—for example, when doing a crossword. But he presented as a man who took pride in his appearance and he was open and co-operative. There was no evidence of psychosis. He appeared to be adjusting to retirement. He scored within the normal range on the hospital anxiety and depression (HAD) scale. He acknowledged that some of his problems were due to retirement and loss of roles.

In January 2006, he learnt that he was being withdrawn from the kidney transplant list owing to the appearance of blood in his faeces. He was unhappy at this. Although his HAD depression score rose to 15, his sertraline was discontinued in the hope that this would eliminate his rectal bleeding and re-open the possibility of a transplant.

The patient returned to the attention of the liaison service in May 2006 when he reported that he was completely unable to remember anything for a full day after his previous dialysis session. This worried him. The possibility of a statin-induced global amnesia was raised. He was given a series of vignettes to read. He reported a few days later that he could identify with these so much that he had discontinued his statin. When reviewed 3 weeks later, he reported no further amnestic bouts and was euthymic.

INVESTIGATIONS

All investigations of mental state were normal at all times other than when his depression score rose briefly after receiving news that he was no longer eligible for a transplant. Physical investigations returned no evidence of triggers to these episodes.

DIFFERENTIAL DIAGNOSIS

The patient’s treating team considered the possibility of a depressive disorder or anxiety disorder but rejected these as explanations for his amnestic episodes.

TREATMENT

The patient had been on 10 mg rosuvastatin. This was stopped. His difficulties cleared on discontinuation of treatment and he remained symptom free thereafter.

OUTCOME AND FOLLOW-UP

Over the following 9 months, the patient had considerable physical and mental stress. His physical condition worsened. After transplant was conclusively ruled out, he was very dispirited. He died 9 months after the events above. But despite the difficulties of his situation, there was no further evidence of amnesia, strange behaviours or of depression.

DISCUSSION

This is a first report of what may be transient global amnesia linked to rosuvastatin, although is as likely to be a general problem linked to statin intake. There are reports of possible transient global amnesia linked to simvastatin or pravastatin.1 While this man’s difficulties emerged when simvastatin 20 mg was switched to rosuvastatin 10 mg, this effectively increased the dose of statin and hence the problem may have been a dose-related problem general to all statins rather than a specific problem linked to rosuvastatin. The problem resolved with discontinuation of statin treatment. While depression and anxiety remain possible explanations for the difficulties this man experienced, he does not appear to have had a clear-cut depressive disorder and ongoing stress did not produce further amnestic episodes. In the absence of physiological disorders on blood testing or other investigations, his renal disease and dialysis do not seem likely candidates as triggers to this problem, although they may have provided contributory stressors.

Transient global amnesia was first described in the late 1950s.2–4 Episodes of global amnesia that are transient have since been described in association with epilepsy and migraine. Brain tumours, trauma or infections have been linked to a global amnesia that may be transient initially but usually progresses to a permanent amnesia. In addition to these disorders, a differential diagnosis must take hysteria, and the likelihood of a concomitant depressive disorder, into account.

More recently, operational criteria have been proposed for transient global amnesia, whereby attacks should be witnessed by an observer, should be accompanied by clear-cut anterograde amnesia, should not be accompanied by clouding of consciousness or other evidence of cognitive disturbances, should not demonstrate focal neurological abnormalities, should show no evidence of epilepsy or head injury, and should resolve within 24 hours.5,6

Our patient had a series of episodes, a number of which were witnessed by an observer. These led to anterograde amnesia. The episodes lasted less than 24 hours. There was no evidence of epilepsy or head injury. There was no clouding of consciousness on either side of the episodes, but it is not clear whether there might have been clouding of consciousness in the course of episodes.

Although not originally linked to drug treatment, transient global amnesia has been linked to treatment with benzodiazepines7 and clioquinol.8 The first cases linked to statin use were reported to regulators in the 1990s, with a first published report in 2001.9 There have been very few published cases, but in 2003 Wagstaffe described 60 cases reports to regulatory authorities; these cases presented equally in men and women, with a mean age of 62 years, although this may be an artefact of the populations to whom statins are prescribed.1 The case reported here maps on to these cases.

Amnesia with benzodiazepines is likely to differ from a statin-related amnesia in that all users of benzodiazepines have some anterograde amnesia but there are no consistent cognitive abnormalities linked to statin intake, and indeed statin use may protect against dementia and amnesia from this source.10

At present it remains unclear whether all cases of transient global amnesia associated with statins resolve fully on discontinuation of treatment. The cardiovascular difficulties for which statins are prescribed could conceivably lead to cognitive difficulties that only come to attention following a more dramatic episode, and which might complicate any assessment as to whether the index problem had resolved. There are no published cases of amnestic difficulties on treatment that clear on dechallenge and reappear on rechallenge. However, in unpublished reports submitted to the regulators, rechallenge appears to reproduce the amnestic problems.1

The mechanisms by which such an effect may be produced remain obscure. But in the interim, the fact that such an effect may be linked to treatment with statins may be of some use to liaison services.

LEARNING POINTS

·  Amnestic behaviours may stem from treatment with statin drugs.

·  Discontinuation of treatment may lead to a full recovery.

·  The problems may be misinterpreted as depressive, anxious or transient ischaemic states.

Competing interests: RM has no competing interests.

Competing interests: SC has no competing interests.

Competing interests: DH has been a speaker for most major pharmaceutical companies but has no links to the use of or marketing of statin drugs.

Patient consent: Patient/guardian consent was obtained for publication.

REFERENCES

1.  Wagstaffe, LR, Mitton, MW, McLendon, B, et al. Statin associated memory loss: analysis of 60 case reports and review of the literature. Pharmacotherapy 2003; 23: 871–80.[CrossRef][Medline]

2.  Bender, MB. Syndrome of isolated episode of confusion with amnesia. J Hillside Hosp 1956; 5: 212–15.

3.  Guyotat, MM, & Courjon, J. Les ictus amnesiques. J Med Lyon 1956; 37: 697–701.[Medline]

4.  Fisher, CM, & Adams, RD. Transient global amnesia. Trans Amer Neurol Assoc 1958; 83: 143–6.

5.  Hodges, JR, & Warlow, CP. Syndromes of transient amnesia: towards a classification. A study of 153 cases. J Neurol Neurosurg Psychiatry 1990; 53: 834–43.[Abstract/FreeFullText]

6.  Quinette, P, Guillery-Guirard, B, Dayan, J, et al. What does transient global amnesia really mean? Review of the literature and thorough study of 142 cases. Brain 2006; 129: 1640–58.[Abstract/FreeFullText]

7.  Morris, HH, & Estes, ML. Traveller’s amnesia. Transient global amnesia secondary to triazolam. JAMA 1987; 258: 945–6.[Abstract]

8.  Mumenthaler, M, Kaesar, HE, Meyer, A, et al. Transient global amnesia after clioquinol. J Neurol Neurosurg Psychiatry 1979; 42: 1084–9.[Abstract/FreeFullText]

9.  Orsi, A, Sherman, O, & Woldeselassie, Z. Simvastatin-associated memory loss. Pharmacotherapy 2001; 21: 767–9.[CrossRef][Medline]

  1. Jick, H, Zornberg, GL, Jick, SS, et al. Statins and the risk of dementia. Lancet 2000; 356: 1627–31.[CrossRef][Medline]